Master of Science (MS)
The aggregation process of amyloid beta from monomeric peptide to oligomers and fibrils is believed to be connected with the neurological disorder Alzheimer’s disease. The focus of this research is the synthesis of alpha, alpha-disubstituted amino acids and peptide inhibitors of amyloid beta aggregation. The inhibitors are designed to interrupt (or alter) this process by binding to amyloid beta’s central hydrophobic core region (residues 17-20, Leucine-Valine- Phenylalanine-Phenylalanine). Target specificity is achieved via self recognition by basing the inhibitors on the sequence in this region. The inclusion of disubstituted amino acids in the sequence of the inhibitors will provide a blocking face (or side) to prevent further disease linked aggregation. This thesis describes the experimental investigations that were conducted to evaluate design elements that can be added to enhance inhibitor designs and methods for improving the synthesis of disubstituted amino acids.
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McCandless, Gregory Todd, "Synthesis of disubstituted amino acids and peptide inhibitors of amyloid beta aggregation" (2008). LSU Master's Theses. 643.
Hammer, Robert P.